PROJECT SUMMARY Neisseria gonorrhoeae, the causative agent of gonorrhea, has developed resistance to every first-line antibiotic since the 1930s, earning it a reputation as the third most important antimicrobial resistant organism.1 Azithromycin-resistance has recently emerged, threatening the CDC?s only recommended treatment regimen ? ceftriaxone plus azithromycin ? and there are few new drugs in the pipeline. Gonorrhea of the throat is important not only for its role in transmission, but also in its role in the development of antibiotic resistance. Thus, all new drugs to treat gonorrhea should be evaluated for their efficacy in treating pharyngeal gonorrhea. Moreover, public health control of resistant gonorrhea relies on assurance that the bacteria have been eradicated. Unfortunately a key piece of data to evaluate treatment efficacy at the throat is missing? when can you reliably trust test of cure by nucleic acid amplification test (NAAT)? NAAT have largely replace culture for diagnosing gonorrhea because they are more sensitive, and easier and quicker to process in the laboratory compared to culture. However, since NAAT detect both viable and non-viable organisms, a positive test result, particularly shortly following treatment, may represent a false-positive. To resolve this unanswered question, we propose a prospective trial of MSM who will swab their throat daily at-home for 21 days using Aptima Combo 2 NAAT following treatment with the standard of care regimen, ceftriaxone and azithromycin. We aim to: 1) Determine the number of days following treatment when Aptima Combo 2 becomes negative for gonorrhea detection for the median and >95% of study population and 2) Identify biologic, microbiologic and socio-behavioral factors associated with time to clearance. We will collect clinical, behavioral and microbiologic data to associate factors with longer times to clearance. Using Kaplan-Meier curves we will determine when the median and >95% of the study population?s NAAT clear, using a strict definition of at least two consecutive negative NAAT. We will use Cox proportional hazards to evaluate biologic and socio-behavioral factors associated with time to clearance. We hypothesize that NAAT clearance will occur at 10 days for >95% of the study population; that higher body mass index, elevated ceftriaxone and/or azithromycin minimal inhibitory concentrations (MIC), chlamydial co-infection at the pharynx and resumption of sexual activity < 7 days after treatment will require more days to clear; and that subjects with ?1 episodes of gonorrhea in the last year will have fewer days of NAAT positivity. The proposed prospective cohort study will provide robust and specific evidence for when to perform a test of cure for gonorrhea at the most difficult to treat anatomic site ? the pharynx. This data will aid researchers in designing new antibiotic treatment trials which are urgently needed and must include efficacy data for pharyngeal infections. Additionally, this evidence will immediately inform the CDC STD Treatment Guidelines recommendations and provide another tool to control the gonorrhea epidemic.